Project Summary/Abstract Adolescent HIV interventions call for more advanced analytic approaches than traditional HIV studies have used. HIV prevention and treatment research trials have traditionally been conducted in a randomized controlled trial (RCT) framework where study participants, often recruited from social service agencies, are randomized into an intervention or standard of care condition and followed over time. Outcome measures consist of self-reported mental health and HIV transmission behaviors. Three large changes are necessary for adolescent studies in the modern era of HIV research. First, youth are often difficult to identify and engage in HIV care. Innovative recruitment strategies that make use of traditional and technology-based methods are necessary to maximize efforts. Second, NIH research priorities target biomedical HIV endpoints. Combination strategies that target HIV end points and comorbid conditions are needed. Lastly, researchers need to plan for intervention delivery in real-world settings. Youth deal with many complex issues, such as homelessness, that can impede access to and delivery of care, directly impacting biological outcome markers. Studies in the proposed U19 proposal will address current challenges in HIV research by using comprehensive youth engagement strategies and combination prevention strategies to address HIV end points and comorbidities. Statistical methods will be used to evaluate interventions in the RCT framework through complex multilevel models (MLM) to evaluate multiple end points over time. In addition, implementation science methods will be used to examine barriers to HIV care and engagement in clinic settings. The Analytic Core provides a range of technological, biomedical, and behavioral research expertise that will support research in the current U19 proposal. The Analytic Core is comprised of statisticians with expertise in fitting complex MLM in HIV studies that contain both biomarker and behavioral outcomes. Technologists are also a part of the Core and have used social media recruitment tools, mobile phone-based assessment, and cloud-based data storage in their own HIV research. The Analytic Core also fields expertise in implementation science and cost effectiveness analysis that will be used to address study aims. The Analytic Core will support research across U19 projects through the following specific aims. First, we will provide consultation on web- based tools that will enhance standard recruitment methods and finalize the recruitment sample of seronegative youth based on risk factors from a larger pool of seronegative youth. Second, data collection will be centralized to maximize data quality and security, minimize costs, and facilitate analysis. Dimagi CommCare software that we have used in prior HIV research will be used and provides an integrated package to provide HIPAA-compliant cloud-based data storage and mobile phone or web-based data entry. Third, Core scientists will conduct innovative analyses that include biological, engagement, and behavioral outcomes. Lastly, the Analytic Core will coordinate with the Management Core for timely dissemination of study findings.